Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Correlation of Polymorphisms of Lipoprotein Lipase (LpL) and Apolipoprotein E (Apo E) With Lipid Profile of Children With Acute Lymphoblastic Eukaemia During Therapy With L - Asparaginase.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04364451
Recruitment Status : Recruiting
First Posted : April 28, 2020
Last Update Posted : April 28, 2020
Sponsor:
Information provided by (Responsible Party):
Maria Ioannidou, Aristotle University Of Thessaloniki

Brief Summary:

Haematological malignancies constitute the most common neoplastic disease in child population, with acute leukemia occupying the number one spot with a percentage of 32.8%. In children, leukaemia is primarily encountered in its acute form (97%) and in the majority of the cases it is presented as Acute Lymphoblastic Leukaemia - ALL (80%). Acute Non-Lymphoblastic Leukemia - ANLL is encountered less frequently (17%) and it includes Acute Myelogenous Leukaemia - AML (15%) and some other rare forms (2%), while the remainder 3% corresponds to chronic leukaemia.

L-Asparaginase (L-ASP) is a fundamental component during the loading phase with regards to achieving remission of the disease and, likewise, during the maintenance phase with the intention of establishing that remission in both children and adults suffering from ALL. The cytotoxic effect of the exogenous administration of Asparaginase is caused by the depletion of the reserve of asparagine in the blood. Asparaginase (ASP) acts as a catalyst for the hydrolysis of asparagine to aspartic acid and ammonia. Asparagine is vital for protein and cell synthesis and, therefore, for their survival. The normal cells of the human body have the ability to produce asparagine from aspartic acid, with the assistance of the enzyme asparagine synthetase. However, the neoplastic cells either lack the enzyme completely or contain minute amounts of it resulting in their inability to synthesize asparagine de novo. The survival of these cells and their ability to synthesize proteins depends entirely on receiving asparagine from the blood. Thus, the administration of ASP leads to the inhibition of DNA, RNA and protein synthesis which, in turn, results in the apoptosis of these cells.

Despite L-ASP's paramount importance in the chemotherapy treatment of leukaemia, it is responsible for a plethora of toxic adverse effects that sometimes even require the termination of its administration. A critical adverse event of ASP is a disorder in the metabolism of lipids. Specifically, it appears that the activation of the endogenous pathway that produces triglycerides through hepatic synthesis leads to hypertriglyceridaemia. The liver is capable of synthesizing VLDL (Very Low Density Lipoproteins) that are rich in triglycerides. Utilising the effect of the enzyme Lipoprotein Lipase (LpL), located on the vascular endothelium, the triglycerides detach from the VLDL causing the latter to transform into IDL (Intermediate Density Lipoproteins) and afterwards into LDL (Low Density Lipoproteins). The triglycerides are later extracted from the blood circulatory system and stored in the adipose tissue, while the LDL particles connect with tissue receptors or macrophage receptors. The final products of the breakdown (coming from the peripheral hydrolysis of triglycerides with the help of LpL) of chylomicrons, VLDL, the remnants of lipoproteins, will eventually be removed by hepatic receptors. Apolipoprotein E (Apo-E) plays an important role in this procedure, it binds these remnants in the presence of LpL and hepatic lipase. Along the duration of the treatment with ASP, reduced LpL functionality is recorded, resulting in impaired plasma clearance of triglycerides and an increase in their levels, while L-ASP appears to cause disorders in other lipid factors, such as cholesterol, HDL and apolipoprotein A. Disorders of lipid metabolism have been found to be associated with polymorphisms of the LpL and Apo-E genes, sometimes with positive and sometimes with negative effects on the lipid profile and more likely participation in cardiovascular complications. The current study will evaluate, the lipid profile of children with ALL, the effect of L-ASP on the lipid profile of the aforementioned patients, as well as the correlation between the polymorphisms of Lipoprotein Lipase (LpL) and Apolipoprotein E (ApoE) with the values of the lipids during chemotherapy. Both the universal and national bibliography that pertain to the effect of ASP on the potency of LpL and App E and to the values of the lipids in children that suffer from ALL during chemotherapy with L-ASP is limited, while there exists no bibliographic reference correlating the genetic background to LpL and Apo E and the relation of the lipid profile. The current study will examine for the first time gene polymorphisms of LpL and Apo E in children with ALL during treatment with ASP.


Condition or disease Intervention/treatment
Acute Lymphoblastic Leukemia Other: Correlation of Polymorphisms of Lipoprotein Lipase (LpL) and Apolipoprotein E (Apo E) With Lipid Profile of Children With Acute Lymphoblastic Leukaemia During Therapy With L - Asparaginase

Show Show detailed description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 90 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Correlation of Polymorphisms of Lipoprotein Lipase (LpL) and Apolipoprotein E (Apo E) With Lipid Profile of Children With Acute Lymphoblastic Leukaemia During Therapy With L - Asparaginase
Actual Study Start Date : September 1, 2019
Estimated Primary Completion Date : August 31, 2022
Estimated Study Completion Date : August 31, 2022



Intervention Details:
  • Other: Correlation of Polymorphisms of Lipoprotein Lipase (LpL) and Apolipoprotein E (Apo E) With Lipid Profile of Children With Acute Lymphoblastic Leukaemia During Therapy With L - Asparaginase
    Children that meet all the inclusion criteria for this study will be examined and undergo treatment with asparaginase (Experimental group) and will be compared to the corresponding teams of healthy children and children that have ailed and are off chemotherapy for at least 6 months (Control group).


Primary Outcome Measures :
  1. The correlation of lipoprotein lipase (LpL) and apolipoprotein E (apoE) polymorphisms with lipid values during the chemotherapy protocol. [ Time Frame: Baseline ]
    The genotypes of children with ALL will be recorded and it might constitute an early indicative factor concerning the treatment's outcome. Thusly, essential information will be extracted about the possible contribution of genotype of children under treatment with L-ASP to the lipid disorder as shown in the lab results, to better monitoring of each unique phase of the therapy for clinical occurrences and complication and to faster therapeutic intervention.

  2. Assessment of the effect of asparaginase by measuring the changes induced in the lipid profile of children with acute lymphoblastic leukaemia. [ Time Frame: Baseline and days 11, 15, 24, 33 in loading phase and days 8, 16, 21 in maintenance phase ]
    During the disease's diagnosis, the lipid profile of the patients' will be determined by measuring the changes of the following parameters compared to the baseline measures: cholesterol (mg/dl), triglycerides(mg/dl), HDL-cholesterol(mg/dl), LDL-cholesterol(mg/dl), apolipoprotein A1(mg/dl), apolipoprotein B100(g/L), lipoprotein α [Lp(α)](nmol/l), glucose (mg/dl), SGOT (U/I), SGPT (U/I), TSH (mU/l) FT4 (pmol/l) amylase (U/I) and lipase (U/I).


Biospecimen Retention:   Samples With DNA
Blood will be collected and placed in a 4ml tube without anticoagulants. The tube will be centrifuged and the blood's serum will be isolated in order to examine the biochemical parameters of the study with the cooperation of the Biochemistry Lab of University Hospital AHEPA. Furthermore, 2ml of whole blood will be collected in a tube containing Ethylenediaminetetraacetic acid (EDTA) as the anticoagulant for use in molecular techniques. The whole blood and the serum will be stored in a temperature of -80 degree Celsius.


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 16 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

Prospective children and adolescents will participate, newly diagnosed with acute lymphoblastic leukaemia, which will be thoroughly tested for a precise and accurate diagnosis of acute leukaemia. Those children will create Team A (Patient Group). Furthermore, an equivalent number of children will participate, of similar ages that have been ailing from ALL and have terminated their chemotherapy for more than 6 months. These children will compose Team B (Control group).

In addition, in the control group (Team C) children will be added of similar ages that have not ailed from ALL (Healthy control group).

Criteria

Inclusion Criteria:

Children and adolescents newly diagnosed with acute lymphoblastic leukaemia. A complete personal and family history will be recorded for each participant from every group with particular emphasis on the presence of dyslipidaemia, early cardiovascular disease or cerebrovascular accident in the individual or in the family. A thorough clinical examination will be performed and the vital signs, blood pressure, weight (kg), height (m) and a Body/Mass Index (BMI) will be recorded and calculate.

The Exclusion criteria are the following:

  • Thyroid Disorder (Abnormal thyroid function)
  • Familial Hypercholesterolemia
  • High Body/ Mass Index (BMI)
  • Administration of corticosteroids some time during the past 2 weeks before diagnosis
  • Administration of total parenteral nutrition before the diagnosis
  • Administration of plasma before the diagnosis
  • Changes or variation of the parameters under study before the start of treatment and the 11th day (before the start of asparagine administration).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04364451


Contacts
Layout table for location contacts
Contact: Maria I Ioannidou, MD, MSc 00306942067923 ioannidou@auth.gr

Locations
Layout table for location information
Greece
Paediatric and Adolescent Haematology-Oncology Unit, 2nd Department of Paediatrics, Aristotle University of Thessaloniki (AUTH), University General Hospital AHEPA Recruiting
Thessaloniki, Greece, 54636
Contact: Maria Ioannidou    00306942067923    ioannidou@auth.gr   
Sponsors and Collaborators
Aristotle University Of Thessaloniki
Investigators
Layout table for investigator information
Study Chair: Emmanuel Hatzipantelis, As.Professor Aristotle University Of Thessaloniki
Layout table for additonal information
Responsible Party: Maria Ioannidou, Principal Investigator, Aristotle University Of Thessaloniki
ClinicalTrials.gov Identifier: NCT04364451    
Other Study ID Numbers: 6225/28-05-2019
First Posted: April 28, 2020    Key Record Dates
Last Update Posted: April 28, 2020
Last Verified: April 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Maria Ioannidou, Aristotle University Of Thessaloniki:
ALL
Children and Adolescents
Polymorphisms of LpL and apoE
Lipid profile
Asparaginase
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Asparaginase
Antineoplastic Agents